Adverse effects associated with acute air pollution exposures have been well-studied; however evidence of chronic exposure effects has been limited. The Harvard Six Cities Study and the American Cancer Society Study are the seminal studies of long-term exposure to air pollution, and both found an increased risk of mortality associated with long-term exposure to particulates. A few recent studies have also shown an association between adverse health outcomes and chronic particulate exposure, even as particulate levels have decreased over time in many areas of the US. However, there are still important gaps in our current knowledge regarding the relative contribution of different size fractions of particulate matter (PM). Effect modification by life style and the identification of susceptible subgroups has been understudied. Answers to these questions would inform targeted public health prevention strategies, as well as environmental policy. In the Nurses' Health Study (NHS), a large prospective cohort study of US women, we have observed increased risks of all-cause and cardiovascular mortality with increasing exposure to PM less than 10 microns in diameter (PM10) among the participants residing in the Northeastern US. These risks were the strongest in obese non-smoking women. In this application we will extend these analyses to include the entire continental US, examine different size fractions of PM (fine [PM2.5] and coarse [PM10-2.5]), evaluate the role of diet and other modifiers on the observed risks, and add in the Health Professional Follow-up (HPFS) Study, a prospective cohort of US men. Diet and physical activity have been shown to be important predictors of cardiovascular disease, and recent studies have suggested that vitamins and nutrients may protect against many of the adverse effects of air pollution. Patterns of distribution in physical activity around the country may have a complex relationship with spatial patterns in air pollution. Therefore, there is much to understand about the potential correlation and/or interaction of physical activity with air pollution. Also, there is strong evidence that there are likely susceptible sub-groups, such as diabetics, the obese, nonsmokers, etc. Due to the extensive prospective information on diet, physical activity, and other lifestyle factors in these two large cohorts, we are in a unique position to explore the impact of a healthy lifestyle on the association of air pollution with cardiovascular mortality. PUBLIC HEALTH RELEVANCE: Particulate matter (PM) attributable to traffic and other combustion sources have been associated with cardiac-related health outcomes and overall mortality. We anticipate that the results of this project will provide novel and comprehensive insights into the effects of chronic exposure to particulates and the relevant size fractions. We also aim to identify susceptible subpopulations and important effect modifiers of the association. These issues are of great public health importance due to the large proportion of the general population exposed to particulate matter.